The objective of this project is to examine the regulation of gene expression and differentiation in neoplasia. Our aim is to identify and characterize both cellular and genetic factors that are important in the neoplastic process. The experimental systems currently under study are: (1) rat hepatoma cell lines at different stages of differentiation; (2) human promyelocytic leukemia cell line (HL60); (3) a variety of undifferentiated human B-cell lymphoma lines of both American and African origin; and (4) virally induced murine erythroleukemia cell lines. The results obtained so far include: (l) construction of cDNA libraries for several hepatoma cell lines, (2) partial cloning of the genes for gamma-glutamyltranspeptidase and epoxide hydrolase form rat liver, (3) characterization of changes in transcriptional levels of alpha-fetoprotein and albumin genes after in vitro treatment of the hepatoma lines with sodium butyrate and dexamethasone, (4) quantitation and characterization of changes in protein synthesis in HL60 accompanying in vitro differentiation induced by 12-0-tetradecanoyl phorbol-13-acetate (macrophage) or by dimethylformamide (granulocyte), and (5) examination of the expression of selected oncogenes in the human B-cell lymphomas.